Closing the disparity gap and optimizing advanced hepatocellular carcinoma care in the hispanic community.

Content available: Author Interview and Audio Recording.

Adipose tissue measurement in clinical research for obesity, type 2 diabetes and NAFLD/NASH.

Introduction: Excess body fat is linked to higher risks for metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease (CV), among other health conditions. However, it is not only the level but also the distribution of body fat that contributes to increased disease risks. For example, an increased level of abdominal fat, or visceral adipose tissue (VAT), is associated with a higher risk of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).

Positive predictive value of sustained virologic response 4 weeks posttreatment for achieving sustained virologic response 12 weeks posttreatment in patients receiving glecaprevir/pibrentasvir in Phase 2 and 3 clinical trials.

Sustained virologic response at posttreatment Week 12 (SVR12) is the widely accepted efficacy endpoint for direct-acting antiviral agents. Those with hepatitis C virus (HCV) are presenting younger with milder liver disease, potentially reducing need for long-term liver posttreatment monitoring. This analysis aimed to determine the positive predictive value (PPV) of SVR at posttreatment Week 4 (SVR4) for achieving SVR12 in patients with HCV, without cirrhosis or with compensated cirrhosis, receiving glecaprevir/pibrentasvir (G/P) in clinical trials.

TVB-2640 (FASN Inhibitor) for the Treatment of Nonalcoholic Steatohepatitis: FASCINATE-1, a Randomized, Placebo-Controlled Phase 2a Trial.

Background & Aims: Increased de novo lipogenesis creates excess intrahepatic fat and lipotoxins, propagating liver damage in nonalcoholic steatohepatitis. TVB-2640, a fatty acid synthase inhibitor, was designed to reduce excess liver fat and directly inhibit inflammatory and fibrogenic pathways. We assessed the safety and efficacy of TVB-2640 in patients with nonalcoholic steatohepatitis in the United States.

Eight Weeks of Treatment With Glecaprevir/Pibrentasvir Is Safe and Efficacious in an Integrated Analysis of Treatment-Naïve Patients With Hepatitis C Virus Infection.

Background & Aims: The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis.

Methods: We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir.

Simeprevir, daclatasvir, and sofosbuvir for hepatitis C virus-infected patients: Long-term follow-up results from the open-label, Phase II IMPACT study.

Background And Aims: Direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection have resulted in high rates of sustained virologic response (SVR) following 8 to 24 weeks of treatment. However, difficult-to-cure/cirrhotic patients typically require a longer treatment duration and less is known regarding the long-term durability of SVR or effect on liver disease progression; to assess this, the IMPACT study followed patients for a 3-year period after end of treatment.

Methods: The Phase II, open-label, nonrandomized IMPACT study assessed the efficacy, safety, and pharmacokinetics of the combination of three DAAs (simeprevir, sofosbuvir, and daclatasvir) in HCV genotype 1/4-infected, treatment-naïve/-experienced cirrhotic patients with portal hypertension or decompensated liver disease.

An HCV-positive recipient of an HCV-positive donor liver successfully treated before and immediately after liver transplant with daclatasvir, sofosbuvir, and ribavirin.

This case suggests that initiation of HCV therapy immediately after liver transplantation with well-tolerated, all-oral regimens may achieve a virologic cure in HCV-positive recipients, thus preventing post-transplant HCV recurrence and associated disease progression. This strategy may broaden utilization of HCV-positive donor livers, potentially including HCV-negative transplant recipients.

Ledipasvir/sofosbuvir-based treatment of patients with chronic genotype-1 HCV infection and cirrhosis: results from two Phase II studies.

Background: Ledipasvir/sofosbuvir ± ribavirin administered for 12 weeks to patients with genotype-1 HCV infection and compensated cirrhosis is effective and well-tolerated. The Phase II TRILOGY-1 and TRILOGY-2 studies investigated whether ledipasvir/sofosbuvir plus the non-nucleotide NS5B inhibitor GS-9669 or the NS3/4A protease inhibitor vedroprevir could reduce treatment duration and/or eliminate the need for ribavirin in genotype-1 HCV-infected patients with compensated cirrhosis.

Methods: In TRILOGY-1, 100 cirrhotic patients were randomized (1:1:1) to 8 weeks of ledipasvir/sofosbuvir plus ribavirin, ledipasvir/sofosbuvir plus GS-9669 250 mg or ledipasvir/sofosbuvir plus GS-9669 500 mg.

Short-duration treatment with elbasvir/grazoprevir and sofosbuvir for hepatitis C: A randomized trial.

Unlabelled: Direct-acting antiviral agents (DAAs) represent the standard of care for patients with hepatitis C virus (HCV) infection. Combining DAAs with different mechanisms may allow for shorter treatment durations that are effective across multiple genotypes. The aim of the C-SWIFT study was to identify the minimum effective treatment duration across multiple genotypes.

Lorcaserin Use in the Management of Morbid Obesity in a Pre-Liver Transplant Patient.

Management of obesity and decompensated cirrhosis in those requiring liver transplantation (LT) is a challenging dilemma. Because of concerns for perioperative complications, many centers avoid transplant in those with a body mass index (BMI) greater than 40 kg/m(2) . Bariatric surgery is associated with increased risk attributable to complications of portal hypertension, including variceal rupture.

Vitamin D Metabolites Inhibit Hepatitis C Virus and Modulate Cellular Gene Expression.

Background And Aims: Previous studies suggest that low serum 25-hydroxyvitamin D [25(OH) D] levels are associated with reduced responsiveness to interferon and ribavirin therapy. We investigated the impact of vitamin D metabolites on HCV and cellular gene expression in cultured hepatoma cells.

Methods: HCV Replicon cell lines stably expressing luciferase reporter constructs (genotype 1b and 2a replicon) or JC1-Luc2a were incubated in the presence of vitamin D2, vitamin D3 or 1,25-dihydroxyvitamin D3 (1,25(OH)2D3).

Sofosbuvir and simeprevir for treatment of hepatitis C virus infection in liver transplant recipients.

Recurrent hepatitis C virus (HCV) infection occurs universally in the allograft in the absence of effective antiviral therapy before liver transplantation (LT). Antiviral therapy with sofosbuvir and simeprevir has proven to be highly effective and well tolerated in the nontransplant setting for treatment of HCV genotype 1 infection; therefore, we sought to evaluate the efficacy and safety of this regimen in LT recipients with recurrent HCV infection. This was a retrospective analysis of a single-center treatment protocol of patients with HCV genotype 1 infection who received a 12-week combination regimen of sofosbuvir and simeprevir.

Efficacy of combination treatment modalities for intermediate and advanced hepatocellular carcinoma: intra-arterial therapies, sorafenib and novel small molecules.

Hepatocellular carcinoma (HCC) is a growing epidemic with a high mortality rate and clear need for improved therapies. In patients with Barcelona-Clinic Liver Cancer (BCLC) B and C, treatment with transarterial chemoembolization (TACE) has been the gold standard in therapy as it delays progression; however, recurrence proves common. In the US, transarterial bead embolization (TABE) has uniformly replaced TACE.

Classical and emerging roles of vitamin D in hepatitis C virus infection.

According to the Institute of Medicine, the risk of clinically significant vitamin D deficiency increases at 25-hydroxyvitamin D levels below 20 ng/mL. By this standard, most cirrhotic hepatitis C virus- (HCV-) positive patients and many noncirrhotic patients are vitamin D-deficient. The high prevalence of vitamin D deficiency among HCV patients is a cause for concern for several specific reasons.

Cross-genotypic polyclonal anti-HCV antibodies from human ascitic fluid.

Many anti-HCV antibodies are available, but more are needed for research and clinical applications. This study examines whether ascitic fluid from cirrhotic patients could be a source of reagent-grade antibodies. Ascitic fluid from 29 HCV patients was screened by ELISA for anti-HCV antibodies against three viral proteins: core, NS4B, and NS5A.

Short communication: Inadequate vitamin D exacerbates parathyroid hormone elevations in tenofovir users.

Parathyroid hormone (PTH) elevations are associated with reduced bone mineral density and adverse health outcomes and have been reported in patients with HIV infection. We aimed to examine the impact of vitamin D status and tenofovir (TDF) use on PTH levels among HIV-infected patients receiving combination antiretroviral therapy (cART). Demographics, medication and supplement use, and clinical data, including 25-hydroxyvitamin D [25(OH)D] and PTH, were collected on 45 HIV-infected men on ART.

Recurrence of primary biliary cirrhosis and development of autoimmune hepatitis after liver transplant: A blind histologic study.

Aim: This long-term study aimed to evaluate recurrence and evolution of primary biliary cirrhosis (PBC) after orthotopic liver transplantation (OLT).

Methods: We reviewed "blindly" allograft biopsy specimens of women who underwent transplantation for PBC (n = 84), and women who received a transplant for chronic hepatitis C virus infection (CHCV ) (n = 108). All needle liver biopsy specimens obtained more than 6 months post-OLT were examined, including 83 specimens from 44 PBC patients and 152 specimens from 58 CHCV patients.

Accelerated hepatitis C virus kinetics but similar survival rates in recipients of liver grafts from living versus deceased donors.

This study tested the hypothesis that hepatitis C virus (HCV) RNA and core antigen levels rise more rapidly after liver transplantation (LT) in recipients of grafts from living donors (LD) versus deceased donors (DD). Eleven consecutive LD and 15 DD recipients were followed prospectively. Before LT, median HCV RNA levels were similar: 5.

Evaluation of fatigue in U.S. patients with primary biliary cirrhosis.

Objectives: Fatigue, which may have a significant impact on quality of life, is the most common reported symptom in primary biliary cirrhosis (PBC). Multiple instruments to quantify fatigue and quality of life in liver disease have been validated, but have not been broadly applied to U.S.

The hepatitis C virus alternate reading frame (ARF) and its family of novel products: the alternate reading frame protein/F-protein, the double-frameshift protein, and others.

The hepatitis C virus (HCV) has an alternate reading frame (ARF) that overlaps the core protein gene. The overlapping reading frame distinguishes HCV from all of its known viral relatives, with the possible exception of GB virus B (GBV-B). The ARF is expressed during natural HCV infections and stimulates specific immune responses.

Mutation Master: profiles of substitutions in hepatitis C virus RNA of the core, alternate reading frame, and NS2 coding regions.

The RNA genome of the hepatitis C virus (HCV) undergoes rapid evolutionary change. Efforts to control this virus would benefit from the advent of facile methods to identify characteristic features of HCV RNA and proteins, and to condense the vast amount of mutational data into a readily interpretable form. Many HCV sequences are available in GenBank.